The mu opioid receptor, the receptor responsible for the actions of morphine, has been widely studied. In recent years, new neuropeptide ligands that act upon the mu opioid receptor have been identified, endomorphin-1 and endomorphin-2. In addition, several new gene products of the mu opioid receptor gene have been reported, MOR1B through MOR1N. These new molecules may be able to provide answers to some long standing questions about the apparent spatial mismatch between the localization of opioid receptors and their endogenous ligands while at the same time giving rise to related questions. For example, despite the distinct anatomical localization reported for endomorphin-1 and endomorphin-2 and the specific pharmacology reported for these neuropeptides, little is known about the biological precursor molecule from which these neuropeptides arise. Also, the newly identified MOR1 variants have not yet been localized to specific cells in the nervous system, particularly in primary afferent neurons. Therefore, we propose to examine the cellular distribution of the MOR1 variants in primary afferent neurons using in situ hybridization and immunohistochemical techniques. In addition, we propose to deepen our understanding of endomorphin immunoreactivity (-ir) by examining the subcellular localization of endomorphin-ir using electron microscopy and identifying peptides and proteins recognized by endomorphin antisera using mass spectrometry. These types of studies are crucial for understanding mu opioid receptor physiology and its implications in pain relief.